TWI478929B - 含２，５，７－經取代唑并嘧啶環之羧酸衍生物 - Google Patents

含２，５，７－經取代唑并嘧啶環之羧酸衍生物 Download PDF

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Publication number: TWI478929B
Authority: TW; Taiwan
Prior art keywords: group; alkyl; phenoxy; ring; dimethyl
Prior art date: 2010-01-13

Application number

TW100100890A

Other languages

English (en)

Chinese (zh)

Other versions

TW201136940A (en

Inventor

Dieter Kadereit

Matthias Schaefer

Stephanie Hachtel

Axel Dietrich

Thomas Huebschle

Andreas Gille

Katrin Hiss

Original Assignee

Sanofi Aventis

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2010-01-13

Filing date

2011-01-11

Publication date

2015-04-01

2011-01-11 Application filed by Sanofi Aventis filed Critical Sanofi Aventis

2011-11-01 Publication of TW201136940A publication Critical patent/TW201136940A/zh

2015-04-01 Application granted granted Critical

2015-04-01 Publication of TWI478929B publication Critical patent/TWI478929B/zh

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BRIOKNPDCPJCOD-UHFFFAOYSA-N [1,3]oxazolo[5,4-d]pyrimidine Chemical class N1=CN=C2OC=NC2=C1 BRIOKNPDCPJCOD-UHFFFAOYSA-N 0.000 title description 9
150000001732 carboxylic acid derivatives Chemical class 0.000 title description 8
150000001875 compounds Chemical class 0.000 claims description 219
-1 cyano, hydroxycarbonyl Chemical group 0.000 claims description 215
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 123
125000001424 substituent group Chemical group 0.000 claims description 123
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 98
125000004432 carbon atom Chemical group C* 0.000 claims description 79
150000003839 salts Chemical class 0.000 claims description 70
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 66
125000004433 nitrogen atom Chemical group N* 0.000 claims description 52
239000000203 mixture Substances 0.000 claims description 50
229910052757 nitrogen Inorganic materials 0.000 claims description 50
229910052799 carbon Inorganic materials 0.000 claims description 48
229910052717 sulfur Inorganic materials 0.000 claims description 47
125000000623 heterocyclic group Chemical group 0.000 claims description 46
229910052760 oxygen Inorganic materials 0.000 claims description 45
229910052736 halogen Inorganic materials 0.000 claims description 40
150000002367 halogens Chemical class 0.000 claims description 39
125000005842 heteroatom Chemical group 0.000 claims description 38
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 37
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 35
229920006395 saturated elastomer Polymers 0.000 claims description 35
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 34
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 29
125000000217 alkyl group Chemical group 0.000 claims description 28
125000002950 monocyclic group Chemical group 0.000 claims description 28
238000000034 method Methods 0.000 claims description 27
125000001153 fluoro group Chemical group F* 0.000 claims description 26
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 25
125000003118 aryl group Chemical group 0.000 claims description 23
150000001412 amines Chemical class 0.000 claims description 21
239000011737 fluorine Substances 0.000 claims description 21
229910052731 fluorine Inorganic materials 0.000 claims description 21
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 20
125000004434 sulfur atom Chemical group 0.000 claims description 20
125000000753 cycloalkyl group Chemical group 0.000 claims description 19
125000003277 amino group Chemical group 0.000 claims description 18
238000002360 preparation method Methods 0.000 claims description 18
125000002619 bicyclic group Chemical group 0.000 claims description 16
125000004093 cyano group Chemical group *C#N 0.000 claims description 16
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 14
125000003342 alkenyl group Chemical group 0.000 claims description 14
125000004430 oxygen atom Chemical group O* 0.000 claims description 14
125000004076 pyridyl group Chemical group 0.000 claims description 14
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 13
125000000304 alkynyl group Chemical group 0.000 claims description 13
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 11
125000005843 halogen group Chemical group 0.000 claims description 11
125000004429 atom Chemical group 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
125000000524 functional group Chemical group 0.000 claims description 9
239000002243 precursor Substances 0.000 claims description 9
239000008194 pharmaceutical composition Substances 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 7
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 7
230000029663 wound healing Effects 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 5
206010012601 diabetes mellitus Diseases 0.000 claims description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
229910052740 iodine Inorganic materials 0.000 claims description 5
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
208000035475 disorder Diseases 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
239000001294 propane Substances 0.000 claims description 3
RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 claims description 3
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 2
208000008960 Diabetic foot Diseases 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
208000011580 syndromic disease Diseases 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
125000003282 alkyl amino group Chemical group 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
125000002887 hydroxy group Chemical group [H]O* 0.000 description 52
238000006243 chemical reaction Methods 0.000 description 36
239000002585 base Substances 0.000 description 33
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 32
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
210000004027 cell Anatomy 0.000 description 25
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 25
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
239000012453 solvate Substances 0.000 description 19
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
102100025750 Sphingosine 1-phosphate receptor 1 Human genes 0.000 description 17
239000000243 solution Substances 0.000 description 17
101000693265 Homo sapiens Sphingosine 1-phosphate receptor 1 Proteins 0.000 description 16
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 15
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
239000000543 intermediate Substances 0.000 description 13
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 13
VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 12
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 12
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 12
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 12
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 11
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
229910052796 boron Inorganic materials 0.000 description 11
239000000460 chlorine Substances 0.000 description 11
229910052801 chlorine Inorganic materials 0.000 description 11
235000019439 ethyl acetate Nutrition 0.000 description 11
DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 description 11
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
239000002253 acid Substances 0.000 description 10
150000001335 aliphatic alkanes Chemical class 0.000 description 10
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
230000004913 activation Effects 0.000 description 9
150000002148 esters Chemical class 0.000 description 9
239000012442 inert solvent Substances 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
229910000027 potassium carbonate Inorganic materials 0.000 description 9
239000011734 sodium Substances 0.000 description 9
239000007858 starting material Substances 0.000 description 9
238000003786 synthesis reaction Methods 0.000 description 9
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
238000004949 mass spectrometry Methods 0.000 description 8
239000012528 membrane Substances 0.000 description 8
229910052708 sodium Inorganic materials 0.000 description 8
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 7
238000005804 alkylation reaction Methods 0.000 description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
229910052794 bromium Inorganic materials 0.000 description 7
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
239000001301 oxygen Substances 0.000 description 7
102000005962 receptors Human genes 0.000 description 7
108020003175 receptors Proteins 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
239000000126 substance Substances 0.000 description 7
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 6
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 6
239000004215 Carbon black (E152) Substances 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
230000029936 alkylation Effects 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
239000003480 eluent Substances 0.000 description 6
235000019253 formic acid Nutrition 0.000 description 6
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 6
229930195733 hydrocarbon Natural products 0.000 description 6
150000002430 hydrocarbons Chemical class 0.000 description 6
150000002576 ketones Chemical class 0.000 description 6
125000001624 naphthyl group Chemical group 0.000 description 6
125000006239 protecting group Chemical group 0.000 description 6
108090000623 proteins and genes Proteins 0.000 description 6
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 5
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical group C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 5
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 5
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 5
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 5
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 5
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 5
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 5
108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 5
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 5
230000002378 acidificating effect Effects 0.000 description 5
150000004703 alkoxides Chemical class 0.000 description 5
238000005576 amination reaction Methods 0.000 description 5
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
239000000872 buffer Substances 0.000 description 5
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
229910000024 caesium carbonate Inorganic materials 0.000 description 5
125000004122 cyclic group Chemical group 0.000 description 5
238000000132 electrospray ionisation Methods 0.000 description 5
125000002541 furyl group Chemical group 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 5
150000007529 inorganic bases Chemical class 0.000 description 5
150000002825 nitriles Chemical class 0.000 description 5
125000006574 non-aromatic ring group Chemical group 0.000 description 5
238000010534 nucleophilic substitution reaction Methods 0.000 description 5
239000012071 phase Substances 0.000 description 5
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
230000019491 signal transduction Effects 0.000 description 5
229910000029 sodium carbonate Inorganic materials 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
239000002904 solvent Substances 0.000 description 5
150000003512 tertiary amines Chemical class 0.000 description 5
238000012360 testing method Methods 0.000 description 5
239000008096 xylene Substances 0.000 description 5
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 4
JBMKAUGHUNFTOL-UHFFFAOYSA-N Aldoclor Chemical class C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC=NS2(=O)=O JBMKAUGHUNFTOL-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 4
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 4
239000000654 additive Substances 0.000 description 4
239000012131 assay buffer Substances 0.000 description 4
125000003943 azolyl group Chemical group 0.000 description 4
239000011324 bead Substances 0.000 description 4
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
125000002843 carboxylic acid group Chemical group 0.000 description 4
238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
238000001816 cooling Methods 0.000 description 4
125000000392 cycloalkenyl group Chemical group 0.000 description 4
238000000752 ionisation method Methods 0.000 description 4
239000007788 liquid Substances 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
210000004698 lymphocyte Anatomy 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
239000000137 peptide hydrolase inhibitor Substances 0.000 description 4
210000002706 plastid Anatomy 0.000 description 4
150000004032 porphyrins Chemical class 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
239000011877 solvent mixture Substances 0.000 description 4
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/424—Oxazoles condensed with heterocyclic ring systems, e.g. clavulanic acid
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A—HUMAN NECESSITIES
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- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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TW100100890A 2010-01-13 2011-01-11 含２，５，７－經取代唑并嘧啶環之羧酸衍生物 TWI478929B (zh)

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EP10305036		2010-01-13

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TW201136940A TW201136940A (en)	2011-11-01
TWI478929B true TWI478929B (zh)	2015-04-01

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TW100100890A TWI478929B (zh)	2010-01-13	2011-01-11	含２，５，７－經取代唑并嘧啶環之羧酸衍生物

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US (1)	US8748436B2 (es)
EP (1)	EP2523958B1 (es)
JP (1)	JP5844277B2 (es)
KR (1)	KR101759117B1 (es)
CN (1)	CN103097392B (es)
AR (1)	AR079981A1 (es)
AU (1)	AU2011206613B2 (es)
BR (1)	BR112012017485A2 (es)
CA (1)	CA2799474C (es)
DK (1)	DK2523958T3 (es)
ES (1)	ES2453956T3 (es)
IL (1)	IL220706A (es)
MX (1)	MX2012007870A (es)
MY (1)	MY156960A (es)
PT (1)	PT2523958E (es)
RU (1)	RU2560876C2 (es)
SG (1)	SG182477A1 (es)
TW (1)	TWI478929B (es)
UY (1)	UY33177A (es)
WO (1)	WO2011086077A1 (es)

Families Citing this family (6)

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AR079980A1 (es)	2010-01-13	2012-03-07	Sanofi Aventis	Derivados de oxazolopirimidina sustituida en 2,5,7
RS53254B (sr) *	2010-01-14	2014-08-29	Sanofi	Derivati karboksilne kiseline sa 2,5-supstituisanim oksazolopirimidinskim prstenom
AU2011206617B2 (en) *	2010-01-14	2015-07-16	Sanofi	2,5-substituted oxazolopyrimidine derivatives
EP2523960B1 (de) *	2010-01-14	2013-10-16	Sanofi	Heterocyclische carbonsäurederivate mit einem 2,5-substituierten oxazolopyrimidinring
US9321787B2 (en)	2011-07-07	2016-04-26	Sanofi	Carboxylic acid derivatives having an oxazolo[5,4-d]pyrimidine ring
EP2990055B1 (en)	2013-04-26	2019-06-05	Kyoto University	Composition comprising a sphingosine-1-phosphate receptor 1 agonist for inhibiting formation and/or enlargement of cerebral aneurysm or for shrinking it

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PL1638551T3 (pl) *	2003-05-19	2012-05-31	Irm Llc	Związki i kompozycje immunosupresyjne
EP1965807A4 (en) *	2005-11-23	2010-10-27	Epix Delaware Inc	S1P RECEPTOR MODULATING COMPOUNDS AND THEIR USE
JP5191497B2 (ja) *	2007-03-21	2013-05-08	エピックスファーマシューティカルズ，インコーポレイテッド	Ｓ１ｐ受容体調節化合物およびその使用
JP5449346B2 (ja)	2008-07-15	2014-03-19	サノフイ	Ｅｄｇ−１受容体アゴニストとしてのオキサゾロピリミジン類
RS53254B (sr)	2010-01-14	2014-08-29	Sanofi	Derivati karboksilne kiseline sa 2,5-supstituisanim oksazolopirimidinskim prstenom
AU2011206617B2 (en)	2010-01-14	2015-07-16	Sanofi	2,5-substituted oxazolopyrimidine derivatives
EP2523960B1 (de)	2010-01-14	2013-10-16	Sanofi	Heterocyclische carbonsäurederivate mit einem 2,5-substituierten oxazolopyrimidinring

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- 2011-01-12 JP JP2012548408A patent/JP5844277B2/ja not_active Expired - Fee Related
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- 2011-01-12 DK DK11700098.4T patent/DK2523958T3/da active
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- 2011-01-12 KR KR1020127021140A patent/KR101759117B1/ko active Active
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WO2009154775A1 (en) *	2008-06-20	2009-12-23	Amgen Inc.	S1p1 receptor agonists and use thereof

Also Published As

Publication number	Publication date
HK1180314A1 (en)	2013-10-18
KR101759117B1 (ko)	2017-07-18
EP2523958A1 (de)	2012-11-21
PT2523958E (pt)	2014-03-27
JP5844277B2 (ja)	2016-01-13
AU2011206613A1 (en)	2012-08-02
KR20120115397A (ko)	2012-10-17
US8748436B2 (en)	2014-06-10
CA2799474A1 (en)	2011-07-21
TW201136940A (en)	2011-11-01
BR112012017485A2 (pt)	2016-04-19
IL220706A (en)	2015-06-30
CN103097392B (zh)	2015-05-13
CA2799474C (en)	2018-02-20
RU2560876C2 (ru)	2015-08-20
WO2011086077A1 (de)	2011-07-21
AR079981A1 (es)	2012-03-07
RU2012134378A (ru)	2014-02-20
MY156960A (en)	2016-04-15
CN103097392A (zh)	2013-05-08
SG182477A1 (en)	2012-08-30
JP2013517239A (ja)	2013-05-16
IL220706A0 (en)	2012-08-30
DK2523958T3 (da)	2014-03-31
US20130079357A1 (en)	2013-03-28
AU2011206613B2 (en)	2015-04-02
EP2523958B1 (de)	2013-12-25
MX2012007870A (es)	2012-07-25
UY33177A (es)	2011-08-31
ES2453956T3 (es)	2014-04-09

Publication	Publication Date	Title
TWI485153B (zh)	2015-05-21	２，５，７－經取代唑并嘧啶衍生物
TWI478929B (zh)	2015-04-01	含２，５，７－經取代唑并嘧啶環之羧酸衍生物
KR101759128B1 (ko)	2017-07-18	２，５-치환된 옥사졸로피리미딘 환을 갖는 카복실산 유도체
CN102834399B (zh)	2015-04-22	具有2,5-取代的*唑并嘧啶环的杂环羧酸衍生物
JP5844278B2 (ja)	2016-01-13	２，５，７−置換されたオキサゾロピリミジン環を有する複素環式カルボン酸誘導体
CN103797015B (zh)	2015-12-09	具有噁唑并[5,4-d]嘧啶环的羧酸衍生物
HK1180314B (en)	2016-04-01	Carboxylic acid derivatives having a 2,5,7-substituted oxazolopyrimidine ring

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2019-01-01	MM4A	Annulment or lapse of patent due to non-payment of fees